>> James: Ken, as an associate professor
of molecular and comparative pathobiology.
And Ken today is going to talk about
the body's postal system,
which are called extracellular vesicles.
>> Thanks so much, James,
and thanks to everybody for attending today.
I'm very excited to share with you
some of the work that is coming out of my lab right now
and I'm gonna pull up my screen,
Hope you can all see this,
it'll just take one second
for me to get into the right one here.
So, I wanna tell you about the body's postal system.
And you might notice that my background here
is that of a post office.
This post office is actually quite an antique post office.
It's from Texas, there's a little general store here,
and the reason that I chose this antique post office
is that I feel like we're in a very exciting time right now,
in the field that I'm about to describe to you.
It might be a little bit of the Wild West too,
but we are making progress,
and there's a lot of discovery to be made
and a lot of contributions, I think, to precision medicine.
So, but first of all,
I wanna give you
maybe a little bit of a public service announcement,
as you may know this year is a little bit unusual,
and we're coming towards the time
where we all have to pay our taxes
which normally would have been in the past.
And as I understand it,
this year's tax deadline is on Blursday,
on Julapril the 15th of this great year 2020.
And there are a few things that we have to do
when we pay our taxes.
We've gotta have an envelope here,
a package basically that can be delivered,
we have to have a stamp,
some means of getting it to its destination,
and of course we wanna have something inside.
So just to remind you,
you have to tell the federal government who you are,
you have to make sure
that it gets to the federal government, your tax return,
you have to have the stamp there
to make sure that that happens.
And you don't wanna forget
to include the check, your payment.
This is basically the payload.
So the postal service isn't gonna be handling
a lot of these tax returns in a little while,
but does our body have some similar system
where we can address things
perhaps between different parts of the body?
So in the multicellular organism,
I wanna pose the questions
of what packages could possibly be traced back
to a cell or an organ of origin?
What packages could target then
specific places going to specific addresses?
Can these packages negotiate biological barriers,
like the barrier between our brain and our blood,
for example, between our gut and the blood?
And can these packages actually deliver anything
that would be meaningful?
So I would like to pose to you
that the answer to all these questions
is the extracellular vesicles.
So these are cellular packages.
And I wanna emphasize you know,
that our body does need to communicate,
the parts of our body need to communicate.
So my brain sometimes wants to know
what's happening in my liver
and the liver might wanna know
what's happening in the brain.
And I think all parts of the body
wanna know what's happening in the gut,
because that's where we get our nutrition from,
our food, so that's dinner.
So extracellular vesicles, what are these things?
So extracellular, the word is obvious,
that means that it's outside of the cell.
And a vesicle is kind of like a soap bubble.
So if you make some soap bubbles
or blow some, you know, kids bubbles,
you know what an extracellular vesicle is basically like,
except that the extracellular vesicles
that I'm talking about, have contents in them.
And so displayed on this slide are several cell types.
So we have some mammalian cells at the top,
some bacteria and parasites at the bottom,
and everything here is color coded.
So as you can see, these little particles,
these little packages, the EVs are coming from the cells,
maybe from an internal compartment,
maybe from the surface of the cell,
and they have many, many different names.
So over the years, there have been scores of names
that have been given to these to these particles.
But all together, we can call them extracellular vesicles.
So they are quite diverse.
And I wanna mention this
because that means
that there are a lot of different kinds of packages.
So depending on what you want to deliver,
what kind of a message needs to be delivered in the body,
you might have a different particle.
Here are some EM images,
so these are electron micrograph images,
we're gonna be seeing a lot more beautiful EM,
I think from Cynthia Wahlberg, a little bit later.
But here what we see are some extracellular vesicles
that my lab has purified
and then imaged by electron microscopy.
So these things generally are quite small.
I know there are some that are big,
but they're generally quite small.
They might be about a millionth,
actually a millionth the size of the cell of origin.
And they can have diverse morphology.
So in this image, you can see some
that almost look like footballs,
up here in the upper right,
there are some that actually have
a few membranes inside them,
but for the most part,
they are these spherical particles
that are bound by lipid bilayer
and have contents of the cell
and I think we're gonna hear more
about enveloped viruses like coronavirus
later today as well.
And I would say that enveloped viruses
themselves are EVs
because they are being produced by the cell
using the same biogenesis pathways.
And something that I like to use
when I tell my son about EVs
is that they're basically like Pokeballs.
So if you've ever played the game Pokemon Go,
or really any Pokemon game
you will know about these Pokeballs
that are these balls,
and you can put little pocket monsters inside them
and you can use them to play a game.
So there are different kinds of EVs,
just like there are different kinds of Pokeballs
and somehow Nintendo actually named one of these the EV,
so this is my favorite one.
The EV has been known for a very long time,
we probably had the first inklings of it
back in the 1930s or so.
But I think the first time
that the word extracellular vesicle was used in a paper,
this is actually not a multicellular organism,
but a little golden algae called Ochromonas
and electron microscopy,
this could see that there were extracellular vesicles
budding from the surface of this organism.
And it was just two years later,
when people discovered
that there were extracellular vesicles
being made in the thyroid of bats
that were reawakening from hibernation.
And so this showed us that the effects
of extracellular vesicles
the association with endocrine processes
was really important.
So what is my lab trying to do right now?
We work mostly, not entirely,
but mostly on brain diseases, like Alzheimer's disease.
And so I'm showing you an illustration here
that I hope will help to communicate
how EVs can be involved in precision medicine.
So here we see four different cell types in the brain.
Of course, the neuron is one that everybody knows about,
and they're depicted in blue here.
But there are other cells in the brain too,
some of them even more abundant than neurons.
And they're depicted in yellow, in green, or gray, in red.
And as you can see, for each of these,
these little tiny spears that are coming off of those cells
are EVs that have come from the cells
and so it's kind of like a color coding.
Now, are these really colors?
No, but we can label them with colors,
much like we saw in Antony Rosen's presentation.
The filters that we can use,
the fluorescence labels that we can use
for these things are really important.
And interestingly, the extracellular vesicles
that are found in the brain
can also get outside of the brain,
they can get into the blood,
they can get into the cerebral spinal fluid,
or even the saliva.
So we can track these things in different parts of the body
by using surface markers.
And so I'm showing here
one of the surface markers that we might use
for a particular cell type in the brain.
Now, when these extracellular vesicles
get out of the brain,
we can do a lot to understand
what is happening in the brain.
And here's the study that we did recently
with Alzheimer's disease.
And we actually decided to look at the vesicles
that were in the brain
before we even looked outside the brain,
let's find out what was actually at the source.
And if we did some studies,
some proteomics studies,
so looking at the proteins that are found in the brain,
we could fairly easily
distinguish Alzheimer's disease from control.
And what you see here in these three boxes,
is basically some bioinformatics
that we tried to use to separate
our control brains from the Alzheimer's disease brains.
And as you can see, we did a pretty good job of it
by just using the tissue itself.
Now if we took our EVs, our cellular packages
and purified them partially from the brain,
we still had good separation but not perfect,
but when we took those EVs and made them very pure,
so that we were just looking at those individual particles,
we could completely separate
the Alzheimer's disease from the control.
And this is important because now what we can do
is we can look for keys.
So I've been talking about colors,
we can think of the different kinds of EVs as having colors,
or we could think of them
as having these little keys on their surface.
Keys that betray their origin,
and so I'm not gonna go into the detail
of what each of these is.
But let me just say that we did find multiple keys
that could be used down the road
to assess what is happening in the brain
just by taking a blood sample.
So, not only can we use EVs
to understand what's happening in the brain,
we can also potentially use them to target tissues.
So if we can put something on the surface
of one of these little cellular bubbles,
we could target it to a particular organ
or a particular cell.
And this is like a lock and a key.
So this little key on the surface of the EV
is going to allow it to attach to
and maybe be taken up by a particular cell.
And I just gave a few examples here
of the brain as a tissue, a tumor tissue,
or even individual cell type like a CD for positive T-cell.
So, how do we engineer these things?
We can put different molecules onto EVs
or onto the cells that they come from.
We can load EVs with drugs
that are able to do something
in the tissue that we target.
So this is where we are today.
I think it's a very exciting time.
We might be more in the Pony Express era right now
than in the Space Force era,
but we're moving forward rapidly.
And I just wanted to let you know
there's an international society known as
the International Society for Extracellular Vesicles.
They have about 1500 members,
and we're having our big virtual meeting next month,
July 20 to 22.
If anybody's interested in covering this
or learning more about EVs
and how they can be used in precision medicine,
please contact me,
I'd be happy to get you a pass to be able to attend this.
And so thank you so much for your attention.
I just wanna give the credit for the work that we're doing
to our so called postal workers
and the funding that we receive.
So we have funding from multiple NIH agencies
and also from some private sources.
And finally, I just wanna note,
and I think that James Berger had mentioned this too,
we can't do precision medicine
without diversity and inclusion.
And so I just think that it's extremely important
to remember that precision or personalized,
that means people, and so the people who are doing the work,
as well as the patients need to be considered here.
So thank you all for your attention,
and I'm happy to take any questions.
>> James: Hi, Ken.
Thank you. Great.
So, David Fryer asks,
"Are EVs common to all mammals?
Are they also found in other multicellular,
non-mammalian species like plants or fungi?"
>> Yes, I like that question,
because it lets me talk a little bit more
about that diversity of EVs.
And indeed, we have found EVs
in everything that we have studied.
So all multicellular organisms we think have EVs,
and even single celled organisms,
like I showed with that golden algae,
they also make EVs.
So this communication system,
it seems to be found in all multicellular organisms.
>> James: Okay, well due to time we'll have to move on.
Thank you again very much.
>> Thank you.